Prenatal diagnosis of the fragile X syndrome: loss of mutation owing to a double recombinant or gene conversion event at the FMR1 locus. Issue 11 (November 1997)

• Record Type: Journal Article
• Authors: Losekoot, M; Hoogendoorn, E; Olmer, R; Jansen, C C; Oosterwijk, J C; van den Ouweland, A M; Halley, D J; Warren, S T; Willemsen, R; Oostra, B A; Bakker, E
• Is Part Of: Journal of medical genetics. Volume 34:Issue 11(1997)
• Page Start: 924
• Page End: 926
• Publication Date: 1997-11
• Subjects: Medical genetics -- Periodicals; 616.042
• DOI: 10.1136/jmg.34.11.924
• Languages: English
• ISSNs: 1468-6244

Abstract

Abstract : The fragile X syndrome, an X linked mental retardation syndrome, is caused by an expanded CGG repeat in the first exon of the FMR1 gene. In patients with an expanded repeat the FMR1 promoter is methylated and, consequently, the gene is silenced and no FMR1 protein (FMRP) is produced, thus leading to the clinical phenotype. Here we describe a prenatal diagnosis performed in a female from a fragile X family carrying a large premutation. In chorionic villus DNA of the male fetus the normal maternal CGG allele and a normal pattern on Southern blot analysis were found in combination with the FRAXAC2 and DXS297 allele of the maternal at risk haplotype. A second chorionic villus sampling was performed giving identical results on DNA analysis and, in addition, expression of FMRP was shown by immunohistochemistry. We concluded that the male fetus was not affected with the fragile X syndrome. Subsequent detailed haplotype analysis showed a complex recombination pattern resembling either gene conversion or a double crossover within a 20 kb genomic region.